Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: In vitro validated method and GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 435 (In Vitro Membrane Barrier Test Method for Skin Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
3-chloropropionic acid
EC Number:
203-534-4
EC Name:
3-chloropropionic acid
Cas Number:
107-94-8
Molecular formula:
C3H5ClO2
IUPAC Name:
3-chloropropanoic acid
Details on test material:
- Name of test material (as cited in study report): 3-Chloropropionic Acid (3-CPA)
- Physical state: solid, colorless
- Analytical purity: 98.8%
- Lot/batch No.: DEFM094405
- Storage condition of test material: at room temperature

Test animals

Species:
other: in vitro

Test system

Details on study design:
Preparation of the Test Item:
500 mg of the test substance were evenly distributed directly atop the BIOBARRIER.

Controls:
- Negative control:
Citric Acid (10%) in Aqua dest. (AppliChem, Lot No.: 9H002452)

- Positive control:
Nitric Acid (69%); (AppliChem, Lot No.: 7K002481)

Dose groups:
1.- Negative control: 500 μL Citric Acid (10%) in Aqua dest.
2.- Positive control: 500 μL Nitric Acid (69%)
3.- Test item: Solid, 500 mg

The test was performed on a total of seven BIOBARRIERS per dose group (four BIOBARRIERS for the test item; one each for the positive and negative control and one as color control).

The test was carried out with the CORROSITEX TM Assay Kit (In vitro International; Irvine, CA 92614). Test kits are available for one, two or four test substances.

BIOBARRIER Preparation:
The preparation was completed as least 2 hours prior to running tests. The entire content of the BIOBARRIER diluent was added to the vial of BIOBARRIER matrix powder. The vial was heated to 68 ºC (± 1 ºC) in a water bath under smooth agitation. After complete dissolution (approximately 20 min.) the solution was allowed to sit for 5 min to allow any air bubbles to rise to the surface. 200 μL of the BIOBARRIER were pipetted into each membrane disc. The BIOBARRIERS were set on the tray and kept in the cold (2-8 ºC) for at least two hours.

Categorization Test:
This step established the category of cut-off times for the sample. 100 mg of the test item were added to the tubes labeled Tube A and Tube B. After shaking a color change was observed in either tube and color was matched to the corresponding color charts on the CORROSITEX TM Testing Protocol Poster. Test material having high acid/alkaline reserves are defined as Category 1 materials, while those with low acid/alkaline reserves are defined as Category 2 materials. If no color change had been observed in either tube, CONFIRM reagent was added to Tube B. After shaking, the resulting color was matched to the color chart on the CORROSITEX TM Testing Protocol Poster.

Classification Test:
This step determined the appropriate Packing Group for the test sample. The CDS (Chemical Detection System) vials were warmed to room temperature (17-25 ºC) before using. Vials 1-4 were utilized for sample replicate testing. The vial labeled (+) was utilized for a positive control sample, the vial labeled (-) for a negative control. The vial labeled C served as a CDS color control. One BIOBARRIER disc was added on top of the first vial. 500 mg of the test item were applied evenly on the top of the BIOBARRIER disc and starting time was recorded. This step was repeated for the remaining vials, staggering each start time by e.g. 10 seconds. The start time difference for each vial was subtracted from the final time to determine the net response time. As soon as a reaction had been observed, the time was recorded.

Results and discussion

In vitro

Results
Irritation / corrosion parameter:
other: other: COOROSITEX TM
Value:
6.21
Remarks on result:
other:
Remarks:
Basis: mean (min). Remarks: Corrosive. (migrated information)

In vivo

Irritant / corrosive response data:
The test substance was compatible with the CORROSITEX TM Assay, as assessed in the qualification step. The chemical has been categorized to category1. A direct color change was observed in tube A and the category was read from the CORROSITEX TM color chart.

The mean time required to activate the CDS was 6.21 ± 0.24 min.

Any other information on results incl. tables

Classification Test

 

 

CORROSITEX TM Time (min)

Color change

Consistency change

Replicate 1

6.25

yes

no

Replicate 2

5.83

yes

no

Replicate 3

6.25

yes

no

Replicate 4

6.50

yes

no

Mean± SD

± 0.24

yes

no

 

 

 

 

Positive control

1.33

yes

no

Negative control

108.00

yes

no

 

Applicant's summary and conclusion

Interpretation of results:
Category 1B (corrosive)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In this study under the given conditions the test substance showed corrosive effects. The test substance is classified as "CORROSIVE", subcategory 1B according to the UN GHS, as the mean time to activate the CDS was >3 - 60 min (6.21 ± 0.24 min) (category 1). The test substance is therefore assigned to Packing Group 2 and to EU Risk-Phrase (R34).
Executive summary:

In the present study the skin corrosive potential of 3-Chloropropionic Acid (3-CPA) was analysed. Corrosive chemicals are, dependent on their grade of corrosivity, able to break through the bio-barrier membrane employed in the "In Vitro Membrane Barrier Test (CORROSITEX TM Assay)" and subsequently activate the underlying CDS. Hence, the time necessary to activate the CDS allows to distinguish between corrosive and non-corrosive test substances. Additionally, it is possible to assess the dermal corrosion hazard potential including the subcategorisation of corrosive substances as permitted in the UN GHS (corrosive subcategory 1A, 1B and 1C) and the assignment to EU Risk Phrases (R35, R34, no label).

Hereby, the test item was placed atop of the bio-barrier membrane. CDS activation was assessed as a color change or a change in consistency. The time required to activate the CDS was matched with given thresholds.

In this study under the given conditions the test substance showed corrosive effects. The test substance is classified as "CORROSIVE", subcategory 1B according to the UN GHS, as the mean time to activate the CDS was >3 - 60 min (6.21 ± 0.24 min) (category 1). The test substance is therefore assigned to Packing Group 2 and to EU Risk-Phrase (R34).